YAP1 rs786204849: Genetics and Ocular Coloboma
The rs786204849 variant is an ultra-rare loss-of-function stop-gain alteration located within the YAP1 gene. Published genetic and developmental research links loss-of-function variants at this locus to autosomal dominant ocular coloboma and multi-tissue ocular developmental anomalies. Because current clinical evidence remains limited and shows variable expressivity, carrying the variant indicates an elevated risk profile rather than an absolute diagnosis.
What each genotype means
Typical risk profile
You carry two reference copies of the YAP1 gene at this position. This common genotype does not code for the premature stop codon seen in the loss-of-function variant and is not linked to congenital optic fissure defects. It reflects the standard baseline risk in the general population for ocular development anomalies.
Found in virtually 100% of individuals across global populations.
Elevated risk of ocular coloboma
You carry one copy of the stop-gain loss-of-function variant in the YAP1 gene. Published literature associates heterozygous YAP1 loss-of-function alleles with autosomal dominant ocular coloboma and related optic fissure closure abnormalities, though penetrance may be incomplete and clinical expressivity varies widely among carriers. If you or a family member have questions about developmental eye conditions, consulting an ophthalmologist or clinical geneticist is recommended.
Ultra-rare worldwide, with a minor allele frequency documented at under 0.01% in gnomAD datasets.
Biallelic loss-of-function (unobserved)
Homozygous loss-of-function genotypes at this site have not been documented in living individuals in major reference cohorts like gnomAD. In animal models, complete loss of Yap1 function typically disrupts embryonic survival and multi-organ development. Because this genotype is essentially unobserved in human populations, its clinical manifestations remain theoretical.
Extremely rare to unobserved globally.
What Is rs786204849 and Where Is It Located?
The genetic variant rs786204849 is a single nucleotide alteration situated within the YAP1 gene on chromosome 11. Specifically classified as a stop-gain or nonsense mutation, this change replaces an amino acid codon with a premature translation stop signal. As a result, the cellular machinery terminates protein synthesis prematurely, producing either a truncated, non-functional protein product or triggering nonsense-mediated mRNA decay. This premature stopping mechanism characterizes rs786204849 as a predicted loss-of-function variant, significantly impairing the normal production of full-length protein.
The Biological Role of the YAP1 Gene
YAP1 encodes the Yes-associated protein 1, a key transcriptional co-activator functioning as the downstream effector of the Hippo signaling pathway. The Hippo-YAP pathway governs fundamental cellular processes including proliferation, differentiation, contact inhibition, and organ size regulation. During embryonic development, YAP1 plays an indispensable role in directing cell survival, apical junction stability, and structural morphogenesis. In ocular biology, proper YAP1 activity is critical for guiding the timely closure of the optic fissure, an essential embryological step that completes the structural formation of the eye globe.
Research Associations: Ocular Coloboma and Eye Development
Published literature has identified heterozygous loss-of-function variants in YAP1 in individuals presenting with ocular coloboma, a congenital structural gap in ocular tissues such as the iris, retina, or optic nerve. Some affected pedigrees display isolated coloboma, whereas others present with broader developmental features, including microphthalmia or hearing impairment. Genetic evidence also highlights incomplete penetrance and variable expressivity, meaning some individuals harboring pathogenic YAP1 mutations exhibit mild eye anomalies or no apparent signs at all. Because only a limited number of families have been documented worldwide, scientific certainty surrounding exact clinical outcomes remains limited.
Population Frequency and Inheritance
The rs786204849 variant is exceptionally rare across all human ancestries. In large-scale reference datasets such as the Genome Aggregation Database (gnomAD), the minor allele frequency is below 0.0001, and the variant is entirely absent from many sampled populations. When YAP1-associated developmental phenotypes occur, they follow an autosomal dominant inheritance pattern, meaning that a single altered copy of the gene is sufficient to elevate clinical risk. However, due to its scarcity and incomplete penetrance, detecting this allele in population surveys without specialized clinical phenotyping remains uncommon.
Navigating Genetic Findings and Clinical Context
Direct-to-consumer or exploratory genetic reports identifying rs786204849 must be interpreted with caution. Genetic screening platforms may have lower positive predictive value for ultra-rare variants, meaning secondary clinical-grade sequencing is required to verify the finding. Furthermore, possessing a statistical genetic association does not equal a medical diagnosis or predict visual impairment. Anyone who receives this finding, particularly those with a personal or familial history of congenital eye malformations, should review the information with an ophthalmologist or clinical geneticist rather than attempting self-diagnosis.
How common is this variant?
The rs786204849 variant is ultra-rare across all global populations, with an estimated minor allele frequency below 0.0001 in public datasets like gnomAD, and is absent from most standard ancestry panels.
Frequently asked questions
What is ocular coloboma?
Ocular coloboma is a congenital condition characterized by missing tissue in parts of the eye, such as the iris, retina, or optic nerve. It occurs when the embryonic optic fissure fails to close completely during early fetal development, often resulting in a keyhole-shaped pupil or visual impairment.
Does carrying rs786204849 guarantee vision problems?
No, carrying the variant does not guarantee vision defects. YAP1 variants often exhibit incomplete penetrance and variable expressivity, meaning some individuals with the variant develop typical vision or very mild ocular changes.
Can rs786204849 be detected on commercial DNA tests?
While direct-to-consumer genotyping arrays occasionally include probes for rare variants, their false-positive rate for ultra-rare alleles like rs786204849 is relatively high. Any unexpected rare finding should always be confirmed through certified clinical diagnostic testing.
How is rs786204849 inherited?
YAP1-related developmental ocular conditions follow an autosomal dominant pattern. This means an individual only needs to inherit one copy of the variant from one parent, or acquire it as a new (de novo) mutation, to be at risk.
Sources & further reading
Educational information only, last refreshed 9/13/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs786204849?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29